title: Single-domain antibodies recognize selectively small oligomeric forms of amyloid beta, prevent Abeta-induced neurotoxicity and inhibit fibril formation.
abstract: Neurotoxic oligomers of amyloid beta (Abeta) peptide have been incriminated in the pathogenesis of Alzheimer's disease. Further exploration of this issue has been hampered to this date by the fact that all previously described anti-Abeta antibodies are unable to discriminate between the different conformations of the peptide (oligomers, protofibrils and fibrils). Here, we describe the generation of novel camelid single-chain binding domains (VHHs) that recognizes specifically low molecular-weight (MW) oligomers. Three VHH specific for Abeta were obtained from an immunized alpaca phage display library. Two were able to recognize selectively intraneuronal Abeta oligomers; furthermore, one of them, V31-1, prevented Abeta-induced neurotoxicity and inhibited fibril formation. This study confirms that VHHs may recognize non-conventional epitopes and illustrates their potential for the immunodiagnostic of diseases due to protein accumulation.
authors.affiliation: Unité de Génétique et Biochimie du Développement - CNRS U2581, France. plafaye@pasteur.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Lafaye
authors.forename: Ikbel
authors.initials: I
authors.lastname: Achour
authors.forename: Patrick
authors.initials: P
authors.lastname: England
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: François
authors.initials: F
authors.lastname: Rougeon
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity / Q000276:immunology; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002161:Camelids, New World / Q000276:immunology; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D019151:Peptide Library; D017434:Protein Structure, Tertiary
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D000939:Epitopes; D010446:Peptide Fragments; D019151:Peptide Library